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  • Wolzak, K. (author)

Protein disulfide isomerases as CSF biomarkers for the neuronal response to tau pathology

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023-02-24
  • Wiley,2023

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/325095
  • https://gup.ub.gu.se/publication/325095URI
  • https://doi.org/10.1002/alz.12978DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:152039241URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • IntroductionCerebrospinal fluid (CSF) biomarkers for specific cellular disease processes are lacking for tauopathies. In this translational study we aimed to identify CSF biomarkers reflecting early tau pathology-associated unfolded protein response (UPR) activation. MethodsWe employed mass spectrometry proteomics and targeted immunoanalysis in a combination of biomarker discovery in primary mouse neurons in vitro and validation in patient CSF from two independent large multicentre cohorts (EMIF-AD MBD, n = 310; PRIDE, n = 771). ResultsFirst, we identify members of the protein disulfide isomerase (PDI) family in the neuronal UPR-activated secretome and validate secretion upon tau aggregation in vitro. Next, we demonstrate that PDIA1 and PDIA3 levels correlate with total- and phosphorylated-tau levels in CSF. PDIA1 levels are increased in CSF from AD patients compared to controls and patients with tau-unrelated frontotemporal and Lewy body dementia (LBD). HighlightsNeuronal unfolded protein response (UPR) activation induces the secretion of protein disulfide isomerases (PDIs) in vitro.PDIA1 is secreted upon tau aggregation in neurons in vitro.PDIA1 and PDIA3 levels correlate with total and phosphorylated tau levels in CSF.PDIA1 levels are increased in CSF from Alzheimer's disease (AD) patients compared to controls.PDIA1 levels are not increased in CSF from tau-unrelated frontotemporal dementia (FTD) and Lewy body dementia (LBD) patients.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Vermunt, L. (author)
  • del Campo, M. (author)
  • Jorge-Oliva, M. (author)
  • van Ziel, A. M. (author)
  • Li, K. W. (author)
  • Smit, A. B. (author)
  • Chen-Ploktkin, A. (author)
  • Irwin, D. J. (author)
  • Lemstra, A. W. (author)
  • Pijnenburg, Y. (author)
  • van der Flier, W. (author)
  • Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
  • Gobom, JohanGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xgobjo (author)
  • Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka (author)
  • Visser, P. J. (author)
  • Teunissen, C. E. (author)
  • Tijms, B. M. (author)
  • Scheper, W. (author)
  • Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

Related titles

  • In:Alzheimers & Dementia: Wiley19:8, s. 3563-35741552-52601552-5279

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